title: Clinical correlates and heritability of cystatin C (from the Framingham Offspring Study).
abstract: Cystatin C (CysC) is associated with cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined the clinical correlates and heritability of CysC and determined if associations between CVD risk factors and CysC differed by CKD status. Among Framingham Heart Study offspring (examined from 1998-2001, n = 3,241, mean age 61 years, 54% women), the 95(th) percentile cut-point was developed for CysC in a healthy subset (n = 779) after excluding participants with diabetes, hypertension, low high-density lipoproteins, obesity, smoking, high triglycerides, prevalent CVD, and CKD (as defined by glomerular filtration rate <60 mL/min per 1.73 m(2)). Multivariable logistic regression was used to evaluate the association between CVD risk factors and high CysC (CysC > or =95(th) percentile cut-point). In a family-based subset (n = 1,188), we estimated CysC heritability using the variance-components method. The cut-point for high CysC was 1.07 mg/L. Age, hypertension treatment, low diastolic blood pressure, body mass index, low high-density lipoprotein cholesterol, and smoking were associated with high CysC in multivariable models. These factors and estimated glomerular filtration rate (egFR) explained 39.2% of CysC variability (R(2)). Excluding CKD did not materially change associations. Multivariable-adjusted heritability for CysC was 0.35 (p <0.001). In conclusion, high CysC is associated with CVD risk factors even in the absence of CKD. The strong associations between CysC and CVD risk factors may partially explain why CysC is a strong predictor of incident CVD.
authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Nisha I
authors.initials: NI
authors.lastname: Parikh
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Guo
authors.forename: Sander J
authors.initials: SJ
authors.lastname: Robins
authors.forename: Patrice
authors.initials: P
authors.lastname: Sutherland
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D002908:Chronic Disease; D055316:Cystatin C / Q000097:blood* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D055316:Cystatin C